Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Keywords: acute myeloid leukemia; biomarker; circular RNA (circRNA); microRNA; targeted therapy.

Figure 1

Schematic presentation of the biogenesis and biological functions of circRNAs. CircRNA, circular RNA; U1 snRNP, U1 small nuclear ribonucleoprotein; RBP, RNA-binding protein; IRES, internal ribosome entry sites; m6A, methyl adenosine; eIF4G2, eukaryotic translation initiation factor 4 gamma 2.

Figure 2

Overview of the biological roles of circRNAs in AML. CircRNAs are known to function either as oncogenes or tumor suppressor genes, regulating key cell processes of leukemia cells such as proliferation, apoptosis, cell cycle, stemness, drug resistance, migration, and invasion. CircRNA, circular RNA; AML, acute myeloid leukemia.

Figure 3

Clinical relevance of circRNAs in AML. The first step is sample collection (bone marrow, serum, or plasma) to be used for circRNA detection. Subsequently, dysregulated circRNAs are quantified through molecular techniques. Then, the mechanisms of dysregulated circRNAs in AML pathogenesis are investigated in vivo and in vitro. The dysregulated circRNAs that can act as diagnostic or prognostic biomarkers are selected. Moreover, targeting specific circRNAs may be an attractive treatment strategy. CircRNA, circular RNA; NGS, next generation sequencing; qRT-PCR, real-time quantitative polymerase chain reaction; RNAi, RNA interference; KD, knockdown.